Eighty-five parturients were invited to participate in this study. Five parturients were excluded because of planning for midline incision due to their diagnosis. The remaining 80 parturients were randomized into three arms using block of six randomization until the second interim analysis, at which point the QLB group was terminated. The interim analyses were performed after 10 and 20 women were recruited to each arm. Analysis of Group QLB was terminated early because Kaplan-Meier survival analysis showed the elapsed time between completion of the block and the first administration of postoperative rescue analgesia (pain-free period) to be significantly shorter in Group QLB at the second interim analysis. A CONSORT flow diagram describing the study protocol is shown in Figure a.
Figure a. Consolidated Standards of Reporting Trials (CONSORT) flow
All parturients were singleton pregnancy that underwent cesarean delivery via Pfannenstiel incision. No local anesthetic skin infiltration for QLB placement was required in any of the parturients.
Interim analysis
The first interim analysis revealed the pain-free period to be 2.50 (1.34-3.66) [hours (95%CI)] in Group IT vs. 7.75 (5.68-9.82) in IT+QLB vs. 1.75 (0.33-3.17) in QLB (overall p=0.002). Log-rank test for pairwise analysis revealed the differences in Group IT vs. IT+QLB (p=0.318), IT vs. QLB (p=0.166), and IT+QLB vs. QLB (p<0.001). The mean amount of morphine required during 24 h was 10.70±9.04 mg in Group IT vs. 7.40±10.35 IT+QLB vs. 17.00±5.94 QLB (p=0.057).
Demographic and clinical data at the second interim analysis (after 20 parturients were recruited into each of the 3 arms) are shown in Table 1. Two parturients in Group IT+QLB were excluded from analysis due to conversion to general anesthesia. There were no patients that required additional intraoperative analgesia. The Kaplan-Meier survival curves showing the pain-free periods in all groups are shown in Figure b. The median pain-free period was 2.50 (1.04-3.96) [hours (95% CI)] in Group IT vs. 7.75 (5.67-9.83) IT+QLB vs. 1.75 (0.75-2.75) QLB (overall p<0.001). Log-rank test for pairwise analysis revealed the differences in IT vs. IT+QLB (p=0.486), IT vs. QLB (p=0.019), and IT+QLB vs. QLB (p<0.001). The NRS pain scores both at rest and at movement 4, 6, 12, and 24 h postoperatively between groups were shown in Figure c. The median (min, max) amount of morphine required during 24 hours was 5.5 (0-25) vs. 5.0 (0-36) vs. 16.5 (1-44) mg in IT vs. IT+QLB vs. QLB, respectively (p=0.001). Cumulative morphine use (mg) and demands between groups at 2nd interim analysis are shown in Table 2.
Table 1. Demographic and clinical data at the 2nd interim analysis
Data
|
IT morphine
(n=20)
|
IT morphine with QLB (n=18)
|
QLB
(n=20)
|
p-value
|
Age (yr)
|
32.25±5.26
|
31.06±6.58
|
32.70±6.70
|
0.705
|
Body mass index (kg/m2)
|
27.90±2.98
|
28.92±4.05
|
28.17±4.15
|
0.694
|
Operation
C/S
C/S with TS
|
16 (80.0%)
4 (20.0%)
|
13 (72.2%)
5 (27.8%)
|
16 (80.0%)
4 (20.0%)
|
0.806
|
Operative time (min)
|
57.75±16.18
|
60.28±17.94
|
68.50±15.82
|
0.113
|
Total morphine in 24 hours (mg)
|
5.5 (0-25)
|
5.0 (0-36)
|
17.5 (1-40)
|
<0.001
|
Pruritus
0
1
2
3
|
9 (45.0%)
8 (40.0%)
2 (10.0%)
1 (5.0%)
|
15 (83.3%)
2 (11.1%)
1 (5.6%)
0 (0.0%)
|
20 (100%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
|
0.007
|
PONV
0
1
|
19 (95.0%)
1 (5.0%)
|
18 (100%)
0 (0.0%)
|
20 (100%)
0 (0.0%)
|
0.380
|
Data presented as mean ± standard deviation, number and percentage, or median and range (min, max). A p-value<0.05 indicates statistical significance.
Abbreviations: IT, intrathecal; QLB, quadratus lumborum block; C/S, cesarean section; TS, tubal sterilization; PONV, postoperative nausea and vomiting
Group QLB had significantly higher morphine consumption in 24 hours than both IT (p=0.003) and IT+QLB (p=0.002). There was no significant difference in morphine consumption between IT and IT+QLB (p=1.000).
Group IT had a significantly higher number of patients with pruritus than both IT+QLB (p=0.020) and QLB (p<0.001). There was no significant difference in pruritus between IT+QLB and QLB (p=0.480).
Figure b. Kaplan-Meier plot of time to first request for morphine (pain-free period) at the 2nd interim analysis, Log-rank overall p<0.001 (Abbreviations: IT, intrathecal; QLB, quadratus lumborum block; IV, intravenous; PCA, patient-controlled analgesia; h, hours)
Figure c. Comparison of pain intensity at rest and at movement at the 2nd interim analysis
Table 2. Cumulative morphine use (mg) and cumulative morphine demands at the 2nd interim analysis
|
IT morphine
(n=20)
|
IT morphine with QLB (n=18)
|
QLB
(n=20)
|
p-value
|
PCA morphine delivery (1 dose=1 mg)
|
24 h
|
5.5 (0-25)
|
5 (0-36)
|
16.5 (1-44)
|
0.001a
|
48 h
|
5.5 (0-37)
|
6 (0-40)
|
20 (1-46)
|
0.006b
|
PCA morphine demand
|
24 h
|
5.5 (0-38)
|
5 (0-37)
|
19 (2-65)
|
<0.001a
|
48 h
|
5.5 (0-42)
|
6 (0-39)
|
22.5 (2-67)
|
0.003a
|
Data presented as median and range (min, max). Kruskal-Wallis with Dunn’s post hoc test with significances indicated by: a, both Group IT and IT+QLB vs. QLB, p<0.05, b, IT vs. QLB, p<0.05.
Abbreviations: IT, intrathecal; QLB, quadratus lumborum block; PCA, patient-controlled analgesia
Final analysis
After Group QLB was terminated, Group IT and IT+QLB were continued in order to analyze whether QLB could be effective for improving postoperative analgesia by extending the pain-free period. Randomization was resumed until there were 30 patients allocated to each of the two remaining study groups. Three patients in Group IT and two patients in IT+QLB were excluded from the analysis due to conversion to general anesthesia. Demographic, surgical, morphine requirement, and side effect data are shown in Table 3. The Kaplan-Meier survival curves of pain-free periods revealed a large difference in the first 6 hours then became smaller afterwards. (Figure d) Therefore, more weight was assigned to the early difference using the Gehan-Breslow and Tarone-Ware tests rather than the conventional log-rank test. The median pain-free period or median time to first request for IV-PCA morphine was 2.50 (1.23-3.77) [hours (95% CI)] in Group IT, and 8.02 (5.96-10.07) in IT+QLB (Gehan-Breslow p=0.027 vs. Tarone-Ware p=0.076 vs. log-rank p=0.238). The NRS at 4, 6, 12, and 24 h between groups are shown in Figure e. The proportion of patients without morphine requirement, cumulative morphine use (mg) and demands between groups are shown in Table 4.
Figure d. Kaplan-Meier plot of time to first request for morphine (pain-free period) at the final analysis, Log-rank test: p=0.238 (Abbreviations: IT, intrathecal; QLB, quadratus lumborum block; IV, intravenous; PCA, patient-controlled analgesia; h, hours)
Table 3. Demographic and clinical data at the final analysis
Data
|
IT morphine
(n=27)
|
IT morphine with QLB
(n=28)
|
p-value
|
Age (yr)
|
31.89±4.93
|
30.68±6.11
|
0.424
|
Body mass index (kg/m2)
|
28.76±3.51
|
28.22±3.97
|
0.593
|
Operation
C/S
C/S with TS
|
20 (74.1%)
7 (25.9%)
|
21 (75.0%)
7 (25.0%)
|
0.937
|
Operative time (min)
|
63.89±18.26
|
64.29±18.65
|
0.937
|
Total morphine in 24 hours (mg)
|
5 (0-56)
|
5 (0-36)
|
0.565
|
Pruritus
0
1
2
3
|
15 (55.6%)
9 (33.3%)
2 (7.4%)
1 (3.7%)
|
19 (67.9%)
8 (28.6%)
1 (3.6%)
0 (0.0%)
|
0.605
|
PONV
0
1
|
26 (96.3%)
1 (3.7%)
|
28 (100%)
0 (0.0%)
|
0.491
|
Data presented as mean ± standard deviation, number and percentage, or median and range (min, max). A p-value<0.05 indicates statistical significance.
Abbreviations: IT, intrathecal; QLB, quadratus lumborum block; C/S, cesarean section; TS, tubal sterilization; PONV, postoperative nausea and vomiting
Figure e. Comparison of pain intensity at rest and at movement at the final analysis
Table 4. The proportion of patients without morphine requirement, cumulative morphine use (mg) and cumulative morphine demands at the final analysis
|
IT morphine
(n=27)
|
IT morphine with QLB (n=28)
|
p-value
|
Without morphine requirement: n (%)
|
6 h
|
10 (37%)
|
21 (75%)
|
0.005
|
8 h
|
10 (37%)
|
15 (53.6%)
|
0.218
|
10 h
|
8 (29.6%)
|
12 (42.8%)
|
0.308
|
12 h
|
8 (29.6%)
|
10 (35.7%)
|
0.631
|
24 h
|
4 (14.8%)
|
4 (14.3%)
|
0.956
|
PCA morphine delivery
|
24 h
|
5 (0-56)
|
4.5 (0-36)
|
0.548
|
48 h
|
7 (0-78)
|
6.5 (0-44)
|
0.768
|
PCA morphine demand
|
24 h
|
6 (0-61)
|
4.5 (0-37)
|
0.494
|
48 h
|
8 (0-84)
|
6.5 (0-39)
|
0.933
|
Data presented as n (%), median and range (min, max). Chi-square test and Mann-Whitney U test were used and a p-value<0.05 indicates statistical significance.
Abbreviations: IT, intrathecal; QLB, quadratus lumborum block; PCA, patient-controlled analgesia
No patients in Group QLB experienced pruritus compared with other two groups (55% in Group IT and 16.7% in IT+QLB) at the 2nd interim analysis (Table 1). However, the number of parturients who experienced postoperative nausea and vomiting was comparable among the study groups. All patients had a sedation score of either 0 or 1. No respiratory depression was observed in any study patient. No parturients experienced muscle weakness of the lower extremities or sign of local anesthetic systemic toxicity from QLB.